Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes

Yuxiang Dong, Yuanqing Tang, Jacques Chollet, Hugues Matile, Sergio Wittlin, Susan A. Charman, William N. Charman, Josefina Santo Tomas, Christian Scheurer, Christopher Snyder, Bernard Scorneaux, Saroj Bajpai, Scott A. Alexander, Xiaofang Wang, Maniyan Padmanilayam, Srinivasa R. Cheruku, Reto Brun, Jonathan L. Vennerstrom

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Based on the structures of several lipophilic trioxolane antimalarial prototypes, we set out to determine which functional groups were associated with good antimalarial profiles and identify more polar (lower Log P/Log D) lead compounds with good physicochemical properties. More lipophilic trioxolanes tended to have better oral activities than their more polar counterparts. Trioxolanes with a wide range of neutral and basic, but not acidic, functional groups had good antimalarial profiles.

Original languageEnglish (US)
Pages (from-to)6368-6382
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number18
DOIs
StatePublished - Sep 15 2006

Keywords

  • 1,2,4-Trioxolane
  • Antimalarial
  • Artemisinin
  • Secondary ozonide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Dong, Y., Tang, Y., Chollet, J., Matile, H., Wittlin, S., Charman, S. A., Charman, W. N., Tomas, J. S., Scheurer, C., Snyder, C., Scorneaux, B., Bajpai, S., Alexander, S. A., Wang, X., Padmanilayam, M., Cheruku, S. R., Brun, R., & Vennerstrom, J. L. (2006). Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes. Bioorganic and Medicinal Chemistry, 14(18), 6368-6382. https://doi.org/10.1016/j.bmc.2006.05.041